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The Role of the Metabolic Acidosis in the Development of Chronic Pancreatitis

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The Role of the Metabolic Acidosis in the Development of Chronic Pancreatitis SMGr up The Role of the Metabolic Acidosis in the Development of Chronic Pancreatitis Peter Melamed* and Felix Melamed Biotherapy Clinic of San Francisco, USA *Corresponding author: Peter Melamed, Biotherapy Clinic of San Francisco, 2215 Post Street, Suite 1, San Francisco, CA 94115, USA, Tel: +1 415 3776643; Fax: +1 415 4093909; Email: [email protected] Published Date: August 10, 2015 ABSTRACT Three main, interrelated reasons for widespread digestive disorders in the modern world might be a low exocrine pancreatic function, chronic metabolic acidosis, and intestinal dysbiosis. Chronic metabolic acidosis generally distresses two alkaline digestive glands: the liver, and pancreas, which secrete alkaline bile and pancreatic juice with a great amount of bicarbonate. The acidic shift in the pH of bile and pancreatic juice can lead to serious biochemical/biomechanical problems. The pancreatic digestive enzymes require an alkaline milieu function properly; therefore, low pH disables their activity. This may be the critical cause of indigestion. Reduction, the pH of the pancreatic juice, can initiate the premature activation of the proteolytic enzymes within the antimicrobial activity, promoting intestinal dysbiosis and makes pancreas vulnerable to infection. pancreas, potentially leading to pancreatitis. Acidification of the pancreatic juice diminishes its bile acids, which irritate the entire biliary system. An aggressive combination of the acidic bile The acidification of bile generates bile stone formation and leads to precipitation of the aggressive and the pancreatic juice can create irregular spasms of the duodenum’s walls and consequent bile calcium from bones to neutralize acidic shift in the blood. It can create calcinosis of the inner reflux into the stomach and the esophagus. The metabolic acidosis forces organism to withdraw organs including pancreas. Chronic Pancreatitis: Recent Advances | www.smgebooks.com 1 Copyright Melamed P.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. The normal exocrine pancreatic function is the core of proper digestion. Currently, there is no base homeostasis can be a pathophysiological therapeutic approach for various gastrointestinal efficient and safe treatment for enhancing exocrine pancreatic function. Reinstating normal acid- disorders. Chronic metabolic acidosis could be a culprit for early stages of chronic pancreatitis and a range of functional gastrointestinal disorders. INTRODUCTION The interrelated combination of chronic metabolic acidosis, low exocrine pancreatic function, and intestinal dysbiosis can explain the widespread digestive disorders in the modern world. Altogether, these causes create a vicious circle [1]. There is not enough time for genetics to be implicated in these disorders; therefore, many scientists and doctors pay attention to environmental factors, such as food, water, stress, lifestyles, toxic chemicals, alcohol consumption, and the inner ecology. functioning of the body. Optimal health depends on the body’s ability to maintain a slightly The acid-base balance, or the acidity/alkalinity balance, is a critical factor in the health and alkaline state. PATHOPHYSIOLOGY OF METABOLIC ACIDOSIS Normally, blood is slightly alkaline, with a pH range of 7.35 to 7.45. The constancy of the blood pH is crucial to the body’s ability to maintain a relatively stable internal environment. Its importance is revealed by the fact that a human being cannot exist if the blood’s pH goes below 7.0 or above 8.0. For instance, blood with a pH of 6.95, which is only slightly acidic, can lead to coma and death. Many body functions are designed to control the acid-base balance, including respiration, digestion, circulation, excretion, and cellular metabolism. The acid-alkaline regulation systems balance. are interrelated and work together to prevent acute or chronic changes in the body’s acid-base What causes the body to be over acidic? The main persistent factors are: • The creation of too many acidic materials by human cells. For instance, the end products of cellular metabolism are amino acids, fatty acids, carbonic, and lactic acids. • an intensive, constant, fermentation process through the release of lactic acid, toxic alcohols, and Intestinal dysbiosis (candidiasis and SIBO-small intestine bacterial overgrowth) causes other acidic compounds. • Diet-induced chronic metabolic acidosis caused by the consumption of processed foods, red• meat, sugars, white flour and rice, and others. environmental chemicals, and others. Chronic toxicity caused by acid-forming compounds, such as alcohol, some medications, Chronic Pancreatitis: Recent Advances | www.smgebooks.com 2 Copyright Melamed P.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. • Dysfunction of the lungs, kidneys, skin, liver and gastrointestinal organs, which are responsible for releasing acidic radicals. • Dehydration and poor microcirculation. • calcium. Chronic deficiency of the major electrolytes such as sodium, magnesium, potassium, and • buffer. Low capacity of blood buffer systems, and, specifically, the low capacity of bicarbonate The CO2 + 2 + H2 2CO3 + HCO3 -bicarbonate buffer system (or the “bicarbonate buffer”)- is the main buffer system in the Theblood. pH It of works blood as is lungsteady, ↨ CO and humanO ↔ H being ↔struggles H to maintain ↨ kidney. stable state to protect the vital organs, such as the brain, lungs, and heart, which completely stop if the pH in the blood drops even slightly. During metabolic acidosis, human beings make the intelligent choice to survive by saving the life important organs, such as the heart, lungs, and brain at the expense of peripheral most by changes in the blood pH because they manufacture pancreatic juice and bile, which are “less essential” organs and tissues. The alkaline digestive glands pancreas and liver are affected generally highly alkaline solutions. NEGATIVE EFFECT OF METABOLIC ACIDOSIS ON PANCREATIC JUICE, BILE AND THE ENTIRE DIGESTIVE SYSTEM Under normal conditions, the pH of liver bile is 7.5- 8.8, and the pancreatic juice has a pH of 7.1- 8.2 [2]. Consequently, the liver, gallbladder, and pancreas, are the inner organs, directly pancreatic pH in an unhealthy way, leading to serious digestion problems. involved in the body’s acid-base balance. On the other hand, metabolic acidosis alters the bile and - The Importance of the Bicarbonate Ion- HCO 3 (Hydrogencarbonate Ion) To maintain the alkalinity of the pancreatic juice, the bile, the liver, and, particularly, the pancreas are extracted, bicarbonates and minerals from the blood. The bicarbonate content is a key reason for the alkalinity of bile and pancreatic juice. Table 1 : Content of BicarbonateBody's (mEq/Liter) Fluid in humanBicarbonate plasma, pancreatic juice and bile [3,4]. Blood (plasma) 27 Pancreatic Juice 92 -145 Bile 45 As seen in bile, and particularly in pancreatic juice, there is a lot of bicarbonate. The pancreatic bicarbonate output and duodenum pH are strongly interrelated. The interaction of digestive hormones, primarily secretin and cholecystokinin, with the autonomic nervous system regulates Chronic Pancreatitis: Recent Advances | www.smgebooks.com 3 Copyright Melamed P.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for commercial this very complicated mechanism [5-7]. purposes, as long as the author and publisher are properly credited. Ductal HCO 3 - 2+ concentration, -secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca pathologicalThe researchers activation found of protease that pancreas and bile and reflux liver extract[4]. bicarbonate ions mostly from the blood. For instance, intravenously administered bicarbonate labeled with the 11C radioisotope appears rapidly in the pancreatic juice. Experiments showed “most if not all the bicarbonate of pancreatic there is a decreased amount of bicarbonate in the pancreatic juice and bile [6,10,11]. juice must come from plasma” [5,8,9]. There is substantial evidence that in pancreatic disorders Duodenal acidity primarily depends on a lesser amount of bicarbonate in the pancreatic juice is persistently low [6,12]. and bile. In chronic pancreatitis patients with exocrine pancreatic insufficiency, the duodenal pH Table 2: The Optimal pH for the Activity of Pancreatic Digestive Enzymes [13,14]. Pancreatic Digestive Enzymes Enzyme Optimal pH Lipase 8.0 Trypsin 7.8 - 8.7 Amylase 6.7 - 7.0 The pancreatic enzymes work only in the alkaline milieu. Therefore, the acidic milieu in the duodenum where general digestion occurs is a central factor of indigestion. There is also a direct of enzymes [15,16]. connection between the bicarbonate concentration and pancreatic juice flow and the elimination Stephen A. McClave, MD, believed that while healthy people have a high bicarbonate concentration in the duodenum, patients with chronic pancreatitis have low bicarbonate lipase stops working
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